George Khoury Lecture

Organized by NIH scientists to honor the memory of Dr. George Khoury, who was highly regarded as a superb scientist and caring mentor of the postdoctoral fellows in his laboratory. This annual lecture is part of the Wednesday Afternoon Lecture Series. Speakers are selected by a committee led by Dr. Eric Freed.

The Lieberman laboratory has been in the forefront of developing RNAi-based therapeutics and using RNAi for genome-wide screening. They were the first to demonstrate that siRNAs could protect mice from disease. They developed methods to harness RNAi to inhibit herpes and HIV transmission in animal models. They have developed strategies for cell-targeted RNAi to treat viral infection, immune disease, and cancer. They are currently investigating tumor-targeted siRNAs for immunotherapy to activate tumor expression of neoantigens and avoid autoimmune side effects of checkpoint inhibitors.

Infection causes 1 in 5 cancers worldwide. Many tumor suppressors, such as p53, have dual functions to prevent tumor cell growth and to inhibit viral replication. These molecules may have evolved from a primordial unicellular eukaryotic antiviral defense system that inhibited DNA synthesis and initiated programmed cell death in response to viral infection. Two cancer viruses found by our lab, Kaposi’s sarcoma herpesvirus and Merkel cell polyomavirus, provide examples of how virus targeting in a cell can be used to understand important circuits controlling tumor cell growth.

The Rice lab focuses on RNA viruses and is well known for its work on hepatitis C. Besides studies aimed at understanding basic viral replicative processes the lab also probes the interface between viruses and host intrinsic and innate immunity and small non-coding RNAs.

The investigation of impeded viral replication in animal cells of particular types or species has uncovered great complexity in the interaction between retroviruses and their hosts. These studies have revealed that cells are equipped with a diverse set of proteins that can directly inhibit the replication of retroviruses, including HIV-1. Genes encoding antiretroviral proteins exhibit unusually high sequence variation, presumably because selection pressures exerted by ancient viral infections have caused them to evolve at an unusually rapid pace.

The Wu laboratory investigates the biochemical basis for histone H2A.Z exchange using the budding yeast model organism. They have identified the yeast SWR1 ATP-dependent chromatin remodeling complex as the responsible enzyme. In a purified system, SWR1 removes H2A-H2B dimers from nucleosomes and deposits free H2A.Z-H2B dimers in an ATP-dependent manner. Homologous enzymes have since been characterized in mammalian systems. How does SWR1 recognize promoters and enhancers genome-wide?